Treatment with the protein biglycan reduces muscle damage in a mouse model of Duchenne and Becker muscular dystrophies (DBMD), according to new research supported, in part, by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dystrophin deficient (mdx) mice given systemic injections of purified biglycan were less susceptible to the loss of muscle strength that characterizes the disease. The study was reported in the Proceedings of the National Academy of Sciences.
Healthy muscle cells contain dystrophin, which stabilizes the cell membrane and helps membrane proteins adhere to matrix proteins outside the cell. But in DBMD, mutations in the dystrophin gene cause the loss of fully functional protein. Although muscle cells also contain a related protein, utrophin, it cannot entirely compensate for the resulting destabilization of the cell membrane that weakens the cell. The new study, led by Justin R. Fallon, Ph.D., professor of neuroscience at Brown University in Providence, R.I., found that the injected biglycan accumulated in skeletal muscle tissue. There, the biglycan was associated with an increased buildup of utrophin at the inner surface of the muscle cell membrane, and matrix protein receptors in the membrane itself. The mice themselves experienced reduced muscle pathology and improved muscle function.
According to the study’s investigators, utrophin could be an attractive target for therapy. The researchers are now moving forward with more studies and hope soon to test whether biglycan treatment might be effective for people with DBMD.
Partial support for the study was also provided by other NIH components, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Eye Institute, the National Institute of Neurological Disorders and Stroke, and the National Center for Research Resources. Other supporters include the Parent Project Muscular Dystrophy, Charley’s Fund and the Nash Avery Foundation.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at https://www.niams.nih.gov.
Amenta AR, Yilmaz A, Bogdanovich S, McKechnie BA, Abedi M, Khurana TS, Fallon JR. Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice. Proc Natl Acad Sci USA. 2011 Jan 11; 108 (2):762-7.